Osteosarcoma: Our study with newly diagnosed localized and metastatic osteosarcoma (OS), in collaboration with several other centers will conclude accrual within the next 4 months. The study is attempting to determine the value of dynamic MRI imaging (DEMRI) is predicting response to neoadjuvant chemotherapy. We now have data on this technique in approximately 20 patients studied at the NCI. While the predictive value appears to be promising, we still need additional data before we can publish this work. We have also performed gene expression profiling analysis on these tumors in collaboration with Dr. Lau at Texas Children's Hospital and preliminary analysis, presented at AACR, suggests that profiles may allow us to cluster patients into "good" and "poor" prognosis prospectively, although once again additional data are required. There is also a suggestion that development of metastatic disease may be predictable based upon expression profiles of the primary tumor. The high-dose chemotherapy with autologous stem cell rescue arm of this study has been closed, as we have now demonstrated that this intervention will not lead to a greater than 50% DFS in poor risk patients. Our plan is to open a new study that will evaluate the use of tariquadar, and MDR1 reversal agent, in combination with standard doses of adriamycin/cisplatin, in newly diagnosed OS patients. If this pilot study proves successful, the plan would be to prospectively determine whether MDR-1 is a viable clinical target in patients with OS. We are also considering several options for recurrent and metastatic patients, including CXCR4 antogonists as well as a kinase inhibitor that has shown activity in metastatic models. We will complete preclinical studies and determine which option to pursue based upon this data. Ewings Sarcoma: We have recently activated a new salvage therapy for recurrent osteosarcoma and Ewing's sarcoma using a combination of sequential gemcitabine/docetaxel based on preliminary in vitro synergy and previous activity of the single agents. This study will be performed through a newly formed sarcoma consortium and is supported by Aventis and Lilly. We have accrued 8 patients to date, and await activation at numerous outside institutions. We are have almost completed accrual of patients with newly diagnosed disease to evaluate the effectiveness of a long-acting G-CSF compound and have opened this study at several other institutions in an effort to complete accrual. Patients receive standard 5-drug chemotherapy and are randomized to receive standard or long-acting G-CSF. This is the only randomized study to evaluate this compound in children and young adults, and we hope to have the study completed and reported within the next year. The long-acting G-CSF continues to appear to be at least equivalent to the standard compound. The COG Ewing's Biology study AEWS02B1 opened in January of 2003, and we continue to receive specimens as a major center participating in this study. We have recently characterized more than 30 specimens using cDNA microarray and are currently analyzing this data. We continue our study using matched related allogeneic transplant for patients with recurrent Ewing's sarcoma and rhabdomyosarcoma. To date 10 patients have been treated. We are continuing in discussions with several other major pediatric transplant centers to consider opening this study at outside sites. We have recently received approval from the DOD to serve at the lead center in another SARC Consortium study evaluating treatment of MPNST patients, in both the sporadic and NF-1 associated setting. We will evaluate the objective response rate of alternating Ifos/etoposide with Adria/Ifos in these patients, followed by surgical resection after 4 cycles of therapy. This study should open for accrual within the next 3 months across the consortium.